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metabolic pathways as possible therapeutic targets for progressive multiple sclerosis

Neural Regeneration Research 2017年第8期12卷 1262-1267页

作者： rebecca m.Heidker mitchell R.Emerson Steven m.Le Vine Department of molecular and Integrative Physiology University of Kansas Medical Center Department of Pharmaceutical Sciences College of Pharmacy-Glendale Midwestern University

Unlike relapsing remitting multiple sclerosis, there are very few therapeutic options for patients with progressive forms of multiple sclerosis. While immune mechanisms are key participants in the pathogenesis of relapsing remitting multiple sclerosis, the mechanisms underlying the development of progressive multiple sclerosis are less well understood. Putative mechanisms behind progressive multiple sclerosis have been put forth： insufficient energy production via mitochondrial dysfunction, activated microglia, iron accumulation, oxidative stress, activated astrocytes, Wallerian degeneration, apoptosis, etc. Furthermore, repair processes such as remyelination are incomplete. Experimental therapies that strive to improve metabolism within neurons and glia, e.g., oligodendrocytes, could act to counter inadequate energy supplies and/or support remyelination. most experimental approaches have been examined as standalone interventions; however, it is apparent that the biochemical steps being targeted are part of larger pathways, which are further intertwined with other metabolic pathways. Thus, the potential benefits of a tested intervention, or of an established therapy, e.g., ocrelizumab, could be undermined by constraints on upstream and/or downstream steps. If correct, then this argues for a more comprehensive, multifaceted approach to therapy. Here we review experimental approaches to support neuronal and glial metabolism, and/or promote remyelination, which may have potential to lessen or delay progressive multiple sclerosis.

关键词： acetyl-coenzyme A carboxylase biotin estrogen iron Kynurenine pathway mitochondria thyroidhormone remyelination stem cells vitamin D

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Rice:Reducing arsenic content by controlling water irrigation

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Journal of Environmental Sciences 2015年第4期27卷 129-131页

作者： Ashley m.Newbigging rebecca E.Paliwoda X.Chris Le University of Alberta

Arsenic has long been recognized as a *** in water supplies that are used for both drinking and crop irrigation can expose many people chronically to elevated levels of arsenic.

关键词： Arsenic Cadmium Rice Food Water irrigation metal contamination

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Testing the potential mechanisms for the maintenance of a genetic color polymorphism in bluefin killifish populations

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Current Zoology 2018年第6期64卷 733-743页

作者： Ashley m.JOHNSON Chia-Hao CHANG rebecca C.FULLER Department of Animal Biology School of Integrative BiologyUniversity of Illinois at Urbana-ChampaignChampaignIL 61820USA

The maintenance of genetic variation in the face of natural selection is a long-standing question in evolutionary *** the bluefin killifish Lucania goodei,male coloration is *** can produce either red or yellow coloration in their anal fins,and both color morphs are present in all *** 2 morphs are heritable and how they are maintained in nature is ***, we tested 2 mechanisms for the maintenance of the red/yellow color *** frequency-dependent mating success predicts that rare males have a mating advantage over common males. Spatial variation in fitness predicts that different color morphs have an advantage in different microhabitat *** a breeding experiment,we tested these hypotheses by creating populations with different ratios of red to yellow males (5 red:1 yellow;1 red:5 yellow)and determining male mating success on shallow and deep spawning *** found no evidence of negative frequency-dependent mating *** morphs tended to have higher mating success, and this was particularly so on shallow spawning ***,on deep substrates,red males enjoyed higher mating success than yellow males,particularly so when red males were rare. However,yellow males did not have an advantage at either depth nor when *** suggest that preference for red males is expressed in deeper water,possibly due to alterations in the lighting ***,male pigment levels were correlated with one another and predicted male mating ***,pigmentation plays an important role in male mating success.

关键词： carotenoid color polymorphism environmental heterogeneity melanin negative frequency dependence pterin

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From micro-to macroevolution:brood parasitism as a driver of phenotypic diversity in birds

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Current Zoology 2020年第5期66卷 515-526页

作者： Iliana medina rebecca m.Kilner Naomi E.Langmore School of BioSciences University of MelbourneVictoria3010Australia Department of Zoology University of CambridgeCambridgeCB23EJUK Division of Ecology and Evolution Australian National UniversityCanberraACT 2600Australia

A fun dame ntal question in biology is how diversity evolves and why some clades are more diverse than *** diversity has often been shown to result from morphological adaptation to different *** role of behavioral interactions as a driver of broadscale phenotypic diversity has received comparatively less *** interactions,however,are a key agent of natural *** behavioral interactions with predators or with parasites can have significant fitness consequences,and hence act as strong evolutionary forces on the phe no type of species,ultimately gen erating diversity betwee n species of both victims and *** obligate brood parasites lay their eggs in the nests of other species,their hosts,and this behavioral interaction between hosts and parasites is often considered one of the best examples of coevolution in the natural *** this review,we use the coevolution between brood parasites and their hosts to illustrate the potential of behavioral interactions to drive evolution of phenotypic diversity at different taxonomic *** provide a bridge between behavioral ecology and macroevolution by describing how this interaction has increased avian phenotypic diversity not only in the brood parasitic clades but also in their hosts.

关键词： brood parasitism coevolution diversity phenotypic variation macroevolution

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Equine-assisted interventions for veterans with servicerelated health conditions: a systematic mapping review

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military medical Research 2020年第2期7卷 174-189页

作者： Adam R.Kinney Aaron m.Eakman rebecca Lassell Wendy Woo Department of Occupational Therapy Colorado State UniversityFort CollinsCO 80523USA Temple Grandin Equine Center Department of Animal SciencesColorado State UniversityFort CollinsCO 80523USA

Background:Evidence-based treatments for service-related health conditions such as posttraumatic stress disorder(PTSD),depression,and traumatic brain injury(TBI)are not effective for all ***-assisted interventions are emerging as an additional treatment modality,but little is known regarding the safe and effective delivery of these *** study aimed to describe the following features of the body of literature concerning equineassisted interventions among veterans:1)veterans who have participated in equine-assisted interventions;2)specific characteristics of equine-assisted interventions in veterans;and 3)the specific characteristics of research on equineassisted interventions in ***:We conducted a systematic mapping review of peer-reviewed literature reporting on equine-assisted interventions among veterans between 1980 and *** of nine databases yielded 3336 unique records,six of which met the inclusion criteria and were *** relevant to the study aims were extracted and ***:Equine-assisted interventions among veterans disproportionately targeted psychosocial outcomes and yielded promising *** detailed methods of EAI varied in the reported studies,ranging from communicating with the horse to mounted *** was also great diversity in outcome *** state of theoretical development regarding the mechanisms by which equine-assisted interventions benefit the veteran population is currently *** provided insufficient detail with respect to the description of the intervention,reasons for attrition,and the dose-response ***:Scientific development of equine-assisted interventions targeting psychosocial outcomes among veterans is warranted to establish their *** outcomes should be expanded,including outcomes more closely aligned with the nature of polytraumatic *** research must also emphasize the theoretical develo

关键词： Veterans Service-related injuries Equine-assisted interventions Posttraumatic stress disorder Systematic mapping review

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Gut microbiome in primary sclerosing cholangitis:A review

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World Journal of Gastroenterology 2020年第21期26卷 2768-2780页

作者： rebecca Little Eytan Wine Binita m Kamath Anne m Griffiths Amanda Ricciuto Division of Gastroenterology Hepatology and NutritionThe Hospital for Sick ChildrenTorontoON M5G 1X8Canada Division of Pediatric Gastroenterology and Nutrition 7-142H Katz Group–Rexall CentreUniversity of AlbertaEdmontonAB T6G 1C9Canada

Primary sclerosing cholangitis(PSC)is a chronic cholestatic liver disease characterized by biliary inflammation and *** of the pathogenesis of PSC in light of its association with inflammatory bowel disease(IBD)and the“gut-liver”axis is an emerging area of interest.A growing number of studies have begun to elucidate the role of the gut microbiota,its metabolites and its influence on host immune responses in the development of PSC and *** of the fecal microbiota have highlighted enriched levels of certain species,including Veillonella,Streptococcus and Enterococcus,among others.A heightened immune response to enteric dysbiosis and bacterial translocation have also been *** example,Klebsiella pneumoniae strains derived from gnotobiotic mice transplanted with PSC-IBD microbiota were found to induce pore formation in human intestinal epithelial cells and enhanced Th17 *** microbes have additionally been hypothesized to be implicated in PSC pathogenesis through their role in the synthesis of various metabolites,including bile acids(BAs),which function as signaling molecules with important gut and hepatic *** expanded knowledge of the gut microbiome as it relates to PSC offers critical insight into the development of microbe-altering therapeutic interventions,such as antibiotics,nutritional interventions and fecal microbial *** of these have already shown some preliminary evidence of *** exciting progress in the field,much work remains to be done;areas that are particularly lacking include functional characterization of the microbiome and examination of pediatric *** this review,we summarize studies that have investigated the microbiome in PSC and PSC-IBD as well as putative mechanisms,including the potential role of metabolites,such as *** then briefly review the evidence for interventions with microbe-altering properties for treating PSC.

关键词： Bile acids Colitis Inflammatory bowel disease microbiome microbiota Primary sclerosing cholangitis

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Transcriptional regulation of secretory capacity by bZip transcription factors

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Frontiers in Biology 2015年第1期10卷 28-51页

作者： rebecca m. FOX Deborah J. ANDREW The Department of Cell Biology The Johns Hopkins University School of Medicine Baltimore MD 21205 USA

Cells of specialized secretory organs expand their secretory pathways to accommodate the increased protein load necessary for their function. The endoplasmic reticulum （ER）, the Golgi apparatus and the secretory vesicles, expand not only the membrane components but also the protein machinery required for increased protein production and transport. Increased protein load causes an ER stress response akin to the Unfolded Protein Response （UPR）. Recent work has implicated several bZip transcription factors in the regulation of protein components of the early secretory pathway necessary to alleviate this stress. Here, we highlight eight bZip transcription factors in regulating secretory pathway component genes. These include components of the three canonical branches of the UPR-ATF4, XBP1, and ATF6, as well as the five members of the Creb3 family of transcription factors. We review findings from both invertebrate and vertebrate model systems suggesting that all of these proteins increase secretory capacity in response to increased protein load. Finally, we propose that the Creb3 family of factors may have a dual role in secretory cell differentiation by also regulating the pathways necessary for cell cycle exit during terminal differentiation.

关键词： bZip transcription factors endoplasmic reticulum Golgi secretion secretory capacity secretory vesicles

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An integrative view of the signaling phenotype： Dynamic links between signals, physiology, behavior and social context

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Current Zoology 2014年第6期60卷 739-754页

作者： maren N. VITOUSEK David m. ZONANA rebecca J. SAFRAN Department of Neurobiology and Behavior Comell University Ithaca New York 14853 USA Department of Ecology and Evolutionary Biology University of Colorado Boulder Colorado 80309 USA

Signal traits are often linked with the physiological state and behavior of their bearer. Direct examination of the causal links among these variables has provided substantial insight into the information content of signals, and into the costs and benefits of signal expression. Yet recent empirical work suggests that the social context in which signals are developed and displayed can play a major role not only in how signals are received, but also in coordinating and mediating the signaling phenotype itself. Here we review both well-established and emerging evidence for direct feedbacks among an individual＇s physiological state, be- havior, and signal elaboration. We then describe an integrative view of signaling that takes into account the bidirectional rela- tionships among components of phenotype and the social context in which signals are developed and displayed. Integrating dy- namic feedback between context and phenotype within models of the evolution and maintenance of signals may yield insights into how signals evolve, how signaling phenotypes are coordinated and maintained on ecological and evolutionary time scales, and how static signals continue to convey relevant phenotypic information about their bearer through time.

关键词： Behavior Phenotype Physiology Signal trait Social feedback Sexual selection

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Decision making for managing Community Flood Risks:Perspectives of United States Floodplain managers

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International Journal of Disaster Risk Science 2021年第5期12卷 649-660页

作者： Jenna Tyler Abdul-Akeem Sadiq Douglas S.Noonan rebecca m.Entress School of Public Administration University of Central FloridaOrlandoFL 32801USA O'Neill School of Public and Environmental Affairs Indiana University–Purdue University IndianapolisIN 46202USA

To reduce flood losses,floodplain managers make decisions on how to effectively manage their community’s flood *** there is a growing body of research that examines how individuals and households make decisions to manage their flood risks,far less attention has been directed at understanding the decision-making processes for flood management at the community *** study aimed to narrow this research gap by examining floodplain managers’perceptions of the quality of their community’s flood management decision-making *** gathered from interviews with 200 floodplain managers in the United States indicate that most floodplain managers perceive their community’s flood management decision-making processes to be *** results also indicate that communities participating in the Federal Emergency management Agency’s Community Rating System,as well as communities with a higher level of concern for flooding and a lower poverty rate,are significantly more likely to report better flood management decision-making processes.

关键词： Community flood risk management Decision making Floodplain managers United States

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Climate drives differences in the germination niche of a globally distributed invasive grass

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Journal of Plant Ecology 2020年第2期13卷 195-203页

作者： rebecca A.Fletcher Kayla m.Varnon Jacob N.Barney Virginia Tech School of Plant and Environmental Sciences675 Old Glade RdBlacksburgVA 24061USA

Aims Exotic invasive species are often exposed to strong selection pressures in their new ranges that can often lead to substantial intraspecific *** differentiation in the timing of life history events in response to climate gradients is thought to be an important mechanism facilitating the range expansion of many invasive *** seed producing plants,the timing of seed germination determines the first environmental conditions experienced by newly emerged germinates,and can have important implications for the successful colonization,establishment and spread of invasive plants—though the role of germination in the success of invasive plants remains poorly *** We assessed the variation in seed germination dynamics among 10 populations of the invasive plant Johnsongrass(Sorghum halepense)across its North American distribution,capturing both a temperature and precipitation gradient,and whether that variation is associated with home *** were exposed to a wide range of temperatures(11–48℃)and two water availability *** Findings We found that Johnsongrass seeds germinated across a wide range of temperatures,but there was substantial variation among populations in the proportion of seeds that germinated in response to both temperature and water *** indicates that as Johnsongrass expanded its range from warmer climates into cooler climates,there was a concurrent shift in the germination temperature niche to cooler *** results suggest that the germination of Johnsongrass seeds has adapted to home climate allowing this invader to maximize germination throughout its range,and that this may be an important contributing factor to its invasion into new environments.

关键词： adaptation among-population variation Johnsongrass Sorghum halepense temperature water availability

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